Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing

Abstract Renowned for their role in haemostasis and thrombosis, platelets are also increasingly recognized for their contribution in innate immunity, immunothrombosis and inflammatory diseases. Platelets express a wide range of receptors, which allows them to reach a variety of activation endpoints...

Full description

Saved in:
Bibliographic Details
Main Authors: Mari Palviainen, Johanna Puutio, Rikke Halse Østergaard, Johannes A. Eble, Katariina Maaninka, Umar Butt, Joseph Ndika, Otto K. Kari, Masood Kamali‐Moghaddam, Kasper Kjaer‐Sorensen, Claus Oxvig, Ana M. Aransay, Juan M. Falcon‐Perez, Antonio Federico, Dario Greco, Saara Laitinen, Yuya Hayashi, Pia R.‐M. Siljander
Format: Article
Language:English
Published: Wiley 2024-10-01
Series:Journal of Extracellular Vesicles
Subjects:
Online Access:https://doi.org/10.1002/jev2.12513
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850251137061486592
author Mari Palviainen
Johanna Puutio
Rikke Halse Østergaard
Johannes A. Eble
Katariina Maaninka
Umar Butt
Joseph Ndika
Otto K. Kari
Masood Kamali‐Moghaddam
Kasper Kjaer‐Sorensen
Claus Oxvig
Ana M. Aransay
Juan M. Falcon‐Perez
Antonio Federico
Dario Greco
Saara Laitinen
Yuya Hayashi
Pia R.‐M. Siljander
author_facet Mari Palviainen
Johanna Puutio
Rikke Halse Østergaard
Johannes A. Eble
Katariina Maaninka
Umar Butt
Joseph Ndika
Otto K. Kari
Masood Kamali‐Moghaddam
Kasper Kjaer‐Sorensen
Claus Oxvig
Ana M. Aransay
Juan M. Falcon‐Perez
Antonio Federico
Dario Greco
Saara Laitinen
Yuya Hayashi
Pia R.‐M. Siljander
author_sort Mari Palviainen
collection DOAJ
description Abstract Renowned for their role in haemostasis and thrombosis, platelets are also increasingly recognized for their contribution in innate immunity, immunothrombosis and inflammatory diseases. Platelets express a wide range of receptors, which allows them to reach a variety of activation endpoints and grants them immunomodulatory functions. Activated platelets release extracellular vesicles (PEVs), whose formation and molecular cargo has been shown to depend on receptor‐mediated activation and environmental cues. This study compared the immunomodulatory profiles of PEVs generated via activation of platelets by different receptors, glycoprotein VI, C‐type lectin‐like receptor 2 and combining all thrombin‐collagen receptors. Functional assays in vivo in zebrafish and in vitro in human macrophages highlighted distinct homing and secretory responses triggered by the PEVs. In contrast, omics analyses of protein and miRNA cargo combined with physicochemical particle characterization found only subtle differences between the activated PEV types, which were insufficient to predict their different immunomodulatory functions. In contrast, constitutively released PEVs, formed in the absence of an exogenous activator, displayed a distinct immunomodulatory profile from the receptor‐induced PEVs. Our findings underscore that PEVs are tunable through receptor‐mediated activation. To truly comprehend their role(s) in mediating platelet functions among immune cells, conducting functional assays is imperative.
format Article
id doaj-art-d1bacf0104064fd49990f7e4e0293c8c
institution OA Journals
issn 2001-3078
language English
publishDate 2024-10-01
publisher Wiley
record_format Article
series Journal of Extracellular Vesicles
spelling doaj-art-d1bacf0104064fd49990f7e4e0293c8c2025-08-20T01:57:59ZengWileyJournal of Extracellular Vesicles2001-30782024-10-011310n/an/a10.1002/jev2.12513Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testingMari Palviainen0Johanna Puutio1Rikke Halse Østergaard2Johannes A. Eble3Katariina Maaninka4Umar Butt5Joseph Ndika6Otto K. Kari7Masood Kamali‐Moghaddam8Kasper Kjaer‐Sorensen9Claus Oxvig10Ana M. Aransay11Juan M. Falcon‐Perez12Antonio Federico13Dario Greco14Saara Laitinen15Yuya Hayashi16Pia R.‐M. Siljander17EV Group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy University of Helsinki Helsinki FinlandEV Group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy University of Helsinki Helsinki FinlandDepartment of Molecular Biology and GeneticsAarhus UniversityAarhusDenmarkInstitute of Physiological Chemistry and PathobiochemistryUniversity of MünsterMünsterGermanyEV Group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy University of Helsinki Helsinki FinlandEV Group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy University of Helsinki Helsinki FinlandDrug Research Program, Faculty of PharmacyUniversity of HelsinkiHelsinkiFinlandDrug Research Program, Faculty of PharmacyUniversity of HelsinkiHelsinkiFinlandDepartment of Immunology, Genetics and Pathology, Science for Life LaboratoryUppsala UniversityUppsalaSwedenDepartment of Molecular Biology and GeneticsAarhus UniversityAarhusDenmarkDepartment of Molecular Biology and GeneticsAarhus UniversityAarhusDenmarkGenome Analysis Platform, Center for Cooperative Research in BiosciencesBasque Research and Technology Alliance (BRTA)MendaroSpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (CIBERehd)MadridSpainFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE); Faculty of Medicine and Health TechnologyTampere UniversityTampereFinlandFinnish Hub for Development and Validation of Integrated Approaches (FHAIVE); Faculty of Medicine and Health TechnologyTampere UniversityTampereFinlandResearch and DevelopmentFinnish Red Cross Blood Service (FRCBS)Helsinki FinlandDepartment of Molecular Biology and GeneticsAarhus UniversityAarhusDenmarkEV Group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy University of Helsinki Helsinki FinlandAbstract Renowned for their role in haemostasis and thrombosis, platelets are also increasingly recognized for their contribution in innate immunity, immunothrombosis and inflammatory diseases. Platelets express a wide range of receptors, which allows them to reach a variety of activation endpoints and grants them immunomodulatory functions. Activated platelets release extracellular vesicles (PEVs), whose formation and molecular cargo has been shown to depend on receptor‐mediated activation and environmental cues. This study compared the immunomodulatory profiles of PEVs generated via activation of platelets by different receptors, glycoprotein VI, C‐type lectin‐like receptor 2 and combining all thrombin‐collagen receptors. Functional assays in vivo in zebrafish and in vitro in human macrophages highlighted distinct homing and secretory responses triggered by the PEVs. In contrast, omics analyses of protein and miRNA cargo combined with physicochemical particle characterization found only subtle differences between the activated PEV types, which were insufficient to predict their different immunomodulatory functions. In contrast, constitutively released PEVs, formed in the absence of an exogenous activator, displayed a distinct immunomodulatory profile from the receptor‐induced PEVs. Our findings underscore that PEVs are tunable through receptor‐mediated activation. To truly comprehend their role(s) in mediating platelet functions among immune cells, conducting functional assays is imperative.https://doi.org/10.1002/jev2.12513extracellular vesiclesfunctional assaysimmunomodulatoryinflammationinnate immunitymacrophages
spellingShingle Mari Palviainen
Johanna Puutio
Rikke Halse Østergaard
Johannes A. Eble
Katariina Maaninka
Umar Butt
Joseph Ndika
Otto K. Kari
Masood Kamali‐Moghaddam
Kasper Kjaer‐Sorensen
Claus Oxvig
Ana M. Aransay
Juan M. Falcon‐Perez
Antonio Federico
Dario Greco
Saara Laitinen
Yuya Hayashi
Pia R.‐M. Siljander
Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
Journal of Extracellular Vesicles
extracellular vesicles
functional assays
immunomodulatory
inflammation
innate immunity
macrophages
title Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
title_full Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
title_fullStr Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
title_full_unstemmed Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
title_short Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
title_sort beyond basic characterization and omics immunomodulatory roles of platelet derived extracellular vesicles unveiled by functional testing
topic extracellular vesicles
functional assays
immunomodulatory
inflammation
innate immunity
macrophages
url https://doi.org/10.1002/jev2.12513
work_keys_str_mv AT maripalviainen beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT johannapuutio beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT rikkehalseøstergaard beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT johannesaeble beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT katariinamaaninka beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT umarbutt beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT josephndika beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT ottokkari beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT masoodkamalimoghaddam beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT kasperkjaersorensen beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT clausoxvig beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT anamaransay beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT juanmfalconperez beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT antoniofederico beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT dariogreco beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT saaralaitinen beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT yuyahayashi beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting
AT piarmsiljander beyondbasiccharacterizationandomicsimmunomodulatoryrolesofplateletderivedextracellularvesiclesunveiledbyfunctionaltesting